Format

Send to

Choose Destination
EMBO Mol Med. 2019 Dec;11(12):e09571. doi: 10.15252/emmm.201809571. Epub 2019 Nov 11.

Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood.

Author information

1
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
2
Department of Clinical Immunology and Transplantology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
3
Fourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
4
Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
5
A. Chelkowski Institute of Physics, University of Silesia, Chorzow, Poland.
6
Silesian Center for Education and Interdisciplinary Research, Chorzow, Poland.

Abstract

Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO-1 independent. Concluding, CoPP increases expression of mobilization-related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation.

KEYWORDS:

CoPP; HO-1; granulocyte colony-stimulating factor; hematopoietic stem and progenitor cells; mobilization

PMID:
31709729
DOI:
10.15252/emmm.201809571
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center